Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract neoplasms.Imatinib is the first-line therapy for GIST patients.Drug resistance limits the long-term effectiveness of imatinib.The regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis.AIM To further investigate the mechanism of IGF2 specific to GISTs.METHODS IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)data.After IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry assays.We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated proteins.We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST.RESULTS Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug resistance.GIST cells with high expression of IGF2 had increased proliferation and migration,invasiveness and EMT.Knockdown of IGF2 significantly inhibited those activities.In addition,OEIGF2 promoted GIST metastasis in vivo in nude mice.IGF2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis.GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance.Moreover,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in GISTs.CONCLUSION IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.

Exosome-transported IncRNA H19 regulates insulin-like growth factor-1 via the H19/let-7a/insulin-like growth factor-1 receptor axis in ischemic stroke

LncRNA(long non-coding RNA) H19 is a transcript of the H19 gene that is expressed during embryogenesis.We previously discove red a role for circular lncRNA H19 in the onset and prognosis of cerebral ischemic stroke.In this study,we used serum from patients with ischemic stroke,and mouse and cell culture models to elucidate the roles of plasma and neuronal exosomes in the regulatory effect of lncRNA H19 on insulin-like growth factor-1 and its mechanism in ischemic stroke,using western blotting,quantitative real-time polymerase chain reaction,and enzyme-linked immunosorbent assays.Plasma exosomal IncRNA H19 was negatively associated with blood levels of insulin-like growth factor-1 in samples from patients with cerebral ischemic stroke.In a mouse model,levels of exosomal IncRNA H19 were positively correlated with plasma and cerebral lncRNA H19.In a cell co-culture model,we confirmed that IncRNA H19 was transported from neuro ns to astrocytes by exosomes to induce downregulation of insulin-like growth factor-1 through the H19/let-7 a/insulin-like growth factor-1 receptor axis.This study provides the first evidence for the transpo rtation of IncRNA H19 by exosomes and the relationship between IncRNA H19 and insulinlike growth factor-1.

RNA interference affects tumorigenicity and expression of insulin-like growth factor-1,insulin-like growth factor-1 receptor,and basic fibroblast growth factor-2 in rat C6 glioma cells

BACKGROUND： Human gliomas are more likely to express basic fibroblast growth factor-2 （FGF-2） insulin-like growth factor-1（IGF-1）, and IGF-1 receptor （IGF-1R） than normal brain tissue. These factors activate signal transduction systems of Ras/MAPK and PI3K/Akl, which promote glioma growth. OBJECTIVE： To utilize RNA interference （RNAi） technique to down-regulate FGF-2, IGF-1, and IGF-1R gene expression, and to investigate the effects of these genes on rat C6 glioma cells, as well as the feasibility of RNAi for treating glioma. DESIGN, TIME AND SETTING： This neurooncological, randomized, controlled, in vivo and in vitro experiment, which used RNAi methodology, was performed at the Laboratory of Molecular Biology, Institute of Biochemistry, Chinese Academy of Sciences between August 2005 and February 2008. MATERIALS： Rat C6 cell lines were purchased from Shanghai Institute of Cellular Biology Affiliated to Chinese Academy of Sciences. Small interfering RNA （siRNA） was synthesized by Shanghai GenePharma. Anti-IGF-1, anti-IGF-1R, anti-FGF-2, anti-mouse and anti-rabbit IgG G1-HRP antibodies were provided by Santa Cruz Biotechnology, USA. Four to six week-old BALB/c nude mice were purchased from the Laboratory Animal Center, Chinese Academy of Sciences. METHODS： C6 glioma cells were transfected with siRNA, which was chemically synthesized in vitro to correspond to endogenous FGF-2, IGF-1, and IGF-1R genes. The inhibition ratio of targeting mRNA expression was detected by semiquantitative RT-PCR, and protein expression was determined by Western blot analysis. C6 glioma cell proliferation was observed using a growth curve C6 glioma cell apoptosis rate and cell cycle were detected by flow cytometry. C6 glioma cell growth regression was observed by transwell migration assay. In addition, nude mouse subcutaneous tumor models were used in this study. For studying the anti-tumor effects of IGF-1 and IGF-1R siRNA, two blank control groups, with six mice each, were set up： A （2.5 μg siRNA was injected one week after C6 cells were inoculated, Le., when tumor volume reached 8 mm × 8 mm） and B （siRNA was injected at the same time with C6 cells were inoculated. To study the effects of FGF-2 siRNA, the groups consisted of a blank control group, negative control group, 2.6 μg siRNA group, 4 μg siRNA group, and 5.3 μg siRNA group, with six mice each. MAIN OUTCOME MEASURES： mRNA and protein inhibition ratio of FGF-2, IGF-1, and IGF-1 R; C6 glioma cell proliferation, apoptosis, and cycle growth arrest; C6 glioma cell growth regression and subcutaneous tumorigenicity rates. RESULTS： All siRNA constructs proved to be effective. After 48 hours, transfection of 200 nmol/L siRNA resulted in a FGF-2 or IGF-1R gene inhibition ratio 〉 80% and an IGF-1 gene inhibition ratio of approximately 70%. Protein expression levels for FGF-2, IGF-1, and IGF-1R decreased in a dose-dependent manner following siRNA transfection, with an inhibition rate 〉 85%, 60%, and 50%, respectively. C6 glioma cell proliferation and apoptosis rates increased in proportion to siRNA. The apoptosis rate of C6 glioma cells induced by FGF-2, IGF-1, and IGF-1R siRNA was 39.96%, 15.07% and 22.47%, respectively （P 〈 0.01）. Transfection of 200 nmol/L IGF or IGF-1R siRNA for 48 hours suppressed C6 glioma cell migration. At 30 days after intratumoral injection of 2.6, 4, and 5.3 tJg FGF-2 siRNA, tumor growth regression rate of FGF-2 siRNA was 56%, 67%, and 86%, respectively. The tumor growth regression rate was 71.88% and 45.71%, respectively, when IGF-1 or IGF-1R siRNA was intratumorally injected 1 week after C6 glioma cell transplantation. When IGF-1 or IGF-1 R siRNA was intratumorally injected during C6 glioma cell transplantation, the tumor growth regression rate was 78.13% and 74.29%, respectively. CONCLUSION： siRNA transfection downregulated gene expression of FGF-2, IGF-1, and IGF-1R In addition, siRNA treatment markedly suppressed glioma cell proliferation, growth, and migration, and concomitantly reduced subcutaneous tumorigenicity.

Insulin-like growth factor-binding protein-3 inhibits IGF-1-induced proliferation of human hepatocellular carcinoma cells

OBJECTIVE Basic fibroblast growth factor(b FGF)and platelet-derived growth factor(PDGF)produced by hepatocellular carcinoma(HCC)cells are responsible for the cell growth.Accumulating evidence shows that insulin-like growth factor-binding protein-3(IGFBP-3)suppresses HCC cell proliferation in both IGF-dependent and independent manners.The present study is to investigate whether treatment with exogenous IGFBP-3 inhibits bF GF and PDGF production and the cell proliferation of HCC cells.METHODS Cell Counting Kit 8 assay were designed to detect HCC cell proliferation,transcription factor early growth response-1(EGR1)involving in IGFBP-3 regulation of b FGF and PDGF were detected by RT-PCR and Western blot assays.Western blot assay was adopted to detect the IGFBP-3 regulating insulin-like growth factor 1 receptor(IGF-1R)signaling pathway.RESULTS The present study demonstrates that IGFBP-3 suppressed IGF-1-induced b FGF and PDGF expression while it does not affect their expression in the absence of IGF-1.To delineate the underlying mechanism,Western-blot and RT-PCR assays confirmed that the transcription factor early growth response protein 1(EGR1)is involved in IGFBP-3 regulation of b FGF and PDGF.IGFBP-3 inhibition of type 1 insulin-like growth factor receptor(IGF1R),ERK and AKT activation is IGF-1-dependent.Furthermore,transient transfection with constitutively activated AKT or MEK partially blocks the IGFBP-3 inhibition of EGR1,b FGF and PDGF expression.CONCLUSION In conclusion,these findings suggest that IGFBP-3suppresses transcription of EGR1 and its target genes b FGF and PDGF through inhibiting IGF-1-dependent ERK and AKT activation.It demonstrates the importance of IGFBP-3 in the regulation of HCC cell proliferation,suggesting that IGFBP-3 could be a target for the treatment of HCC.

Effect of sericin on diabetic hippocampal growth hormone/insulin-like growth factor 1 axis

Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, following which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to alleviate hippocampal damage in diabetic rats.

Preparatory training attenuates drastic response of the insulin-like growth factor binding protein 1 at the point of maximal oxygen consumption in handball players

Background:Intensive exercise changes physiological need for glucose and several biochemical pathways responsible for its metabolism response.Among them are those which involve insulin,insulin-like growth factor(IGF-1),and IGF-binding proteins(IGFBPs).Different types and degrees of exercise,as well as an athlete's fitness,may induce a range of responses regarding concentrations and time needed for the alteration.The idea of the work was to find out whether and how insulin/IGF axis responds to additional physical activity in the already trained subjects and if so,is the adaptation potentially beneficial from the aspect of metabolic control.Methods:The effect of 4-week intensive training on campus(preparatory training) on the levels of insulin,IGF-1,and IGFBPs during maximal progressive exercise test(MPET) on a treadmill was compared to the results obtained during MPET conducted after a regular training season of a female elite handball team(n = 17,age:17 ± 1 years,height:171 ± 8 cm,weight:65 ± 8 kg,body mass index:22 ± 1 kg/m^2 at the beginning of the study;there were no significant changes at the end).Serum samples were obtained from players immediately before the test(basal),at the end of the test after reaching the point of maximal oxygen consumption(VO_(2max)),and after recovery.Results:The concentration of insulin decreased at VO_(2max),but remained higher in players after preparatory training(12.2 ± 2.5 m U/L vs.8.9 ± 4.4 m U/L,p = 0.049).The level of IGFBP-1 decreased in players at VO_(2max) in either case of training,but it remained much higher in tests performed after the preparatory regime than before(p = 0.029).Concentrations of IGF-1,IGFBP-2,-3,and-4 did not change significantly.Conclusion:The inverse relation between insulin and IGFBP-1 was lost during MPET,as these 2 molecules changed in the same direction.The results obtained suggest less severe stress-induced depression of insulin and IGFBP-1 after preparatory training.But another metabolic mechanism cannot be excluded,and that is potentially impaired insulin sensitivity resulting in higher level of IGFBP-1.

ACTR调控IGF-1R对肝癌细胞生长的影响

目的探究ACTR调控IGF-1R的表达对肝癌细胞生长的影响及意义。方法外源性免疫共沉淀、内源性免疫共沉淀检测ACTR与IGF-1R之间的相互作用。应用细胞免疫荧光共定位,检测ACTR与IGF-1R在肝癌细胞内共定位情况。qRT-PCR及Western blot实验,检测肝癌细胞中ACTR对IGF-1R表达的影响。将肝癌细胞系分为阴性对照组、转染ACTR组、敲低IGF-1R组、敲低IGF-1R+转染ACTR组,应用CCK8法测定各组细胞生长情况。结果外源性免疫共沉淀、内源性免疫共沉淀均证实ACTR与IGF-1R之间存在相互作用。细胞免疫荧光共定位证实ACTR与IGF-1R在肝癌细胞内存在共定位表达。qRT-PCR证实敲低ACTR后,IGF-1R mRNA表达水平降低(P<0.05),回转ACTR后IGF-1R mRNA表达水平亦可恢复。Western blot证实敲低ACTR后IGF-1R表达降低,而回转ACTR后IGF-1R表达可恢复。细胞生长曲线说明ACTR能够促进肝癌细胞的生长(P<0.05),当应用siRNA敲低IGF-1R后,ACTR的促细胞生长作用减弱。结论ACTR与IGF-1R之间存在相互的作用,IGF-1R介导了ACTR促进肝癌细胞生长的过程,ACTR/IGF-1R轴在肝癌细胞的生长中发挥了必要的作用,有可能成为治疗肝癌的靶点之一,为肝癌的防治提供新的思路。

Genetic expression of Col-2A and Col-10A as a function of administration of IGF-1 &TGF-<i>β</i>with and without anterior mandibular repositioning appliance on the growth of mandibular condylar cartilage in young rabbit

New Zealand (NZ) young rabbits with the administration of insulin-like growth factor (IGF-1) and transforming growth factor-β (TGF-β) with and without mandibular anterior repositioning appliances are explored for the growth of the mandibular condylar cartilage (MCC). 32 growing NZ and rabbits were divided into 4 groups: the group with saline injection in TMJ, the group which received growth factor injection in TMJ, the group which received anterior positioning appliance and the group which received growth factors injection as well as mandibular repositioning appliance. Gene expression was studied by real-time RT-PCR and cartilage growth by histomorphometry. Administration of growth factors along with mandibular repositioning appliances has induced 1) 1.70-fold expression of Col-2Agene (p value < 0.0005) and 2) 1.47-fold expression of Col-10Agene (p value < 0.0005). In contrast, administration of only mandibular repositioning appliances induced 1) 1.28-fold expression of Col-2Agene (p value < 0.0005) and 2) merely 0.62-fold expression of Col-10Agene (p value < 0.0005), while administration of growth factors only induced 1) mere 0.56-fold expression of Col-2Agene (p value 10A gene (p value growth factors along with mandibular repositioning appliances causes an increase in genetic expressions which have been corroborated by histomorphometry and validated by statistical analysis, during an accelerated growth of mandibular condylar cartilage. Administration of growth factors in the TMJ could provide a synergistic role along with mandibular repositioning appliances for treatment of mandibular retrognathism as well as disorders on the MCC.

二花脸和大白猪的脂肪组织中GH-R、IGF-1和IGF-ⅠR基因表达的发育性变化

分别于出生当天、3、2 0、30、4 5、90、12 0、180日龄随机屠宰二花脸公、母猪各 4头 (30日龄仅有公猪 ) ,于 2 0、30、90、12 0、180日龄随机屠宰大白猪公猪 4头 ,采集背部皮下脂肪组织。用RT PCR方法 ,以 18SrRNA作内标 ,定量分析脂肪组织中生长激素受体 (GH R)、胰岛素样生长因子 1(IGF 1)及胰岛素样生长因子Ⅰ型受体 (IGF ⅠR)基因表达的发育性变化 ,并进行品种和性别间比较。结果表明 :脂肪组织中GH RmRNA的表达有明显的发育性变化及品种差异 ,二花脸母猪GH RmRNA水平出生时较低 ,4 5日龄达到高峰 ,之后维持稳定 ;二花脸公猪GH RmRNA水平在出生时较高 ,至 4 5日龄达到最高值 ,之后显著下降 ,但总体上没有性别差异 ;大白猪公猪GH RmRNA水平极显著低于二花脸公猪 (P <0 0 1)。脂肪组织中IGF 1mRNA的表达有明显的发育性变化及性别和品种差异 ,二花脸母猪显著低于公猪 (P <0 0 5 ) ,大白猪公猪极显著低于二花脸公猪 (P <0 0 1) ;脂肪组织中IGF ⅠRmRNA的表达有明显的发育性变化 ,但在总体上没有明显的性别和品种差异。结果提示 :猪脂肪组织中GH R、IGF 1和IGF ⅠR的基因表达有特定的发育模式 ,IGF 1基因表达的品种差异可能正是两品种猪脂肪沉积规律不同的主要原因之一。

绵羊皮肤中GHR、IGF-1和IGF-1R基因表达的发育性变化及品种特点

采用相对定量反转录多聚酶链式反应（RT-PCR）方法，以18S rRNA作内标，研究了罗米丽（Romilly Hillys）×中国美利奴（新疆军垦型）杂交一代优质细毛羊和哈萨克粗毛羊皮肤中生长激素受体（GHR）、胰岛素样生长因子1（IGF-1）和胰岛素样生长因子1受体（IGF-1R）mRNA发育性变化并进行了品种间比较。分别于30、60、90、135、180和255日龄称重、采毛样，并于30、90、135和255日龄采皮样。结果表明：粗毛羊和细毛羊体重、羊毛生长的发育模式没有明显的差异，30-135日龄体重迅速增加，135～255日龄增重十分缓慢；30-135日龄羊毛日增长逐渐增加，135-180日龄羊毛生长十分缓慢，而180-255日龄又上升到较高水平。粗毛羊皮肤中GHRmRNA在30～90曰龄显著增加（P〈0．05），90日龄达到高峰，此后显著下降（P〈0．05）；细毛羊在135日龄时GHR mRNA极显著地升高（P〈0．01），此后又极显著地下降。粗毛羊皮肤中IGF-1、IGF-1R mRNA30—90日龄上升，90日龄之后极显著下降（P〈0．01）：细毛羊皮肤中IGF—1、IGF-1R mRNA出生时较高，然后逐渐下降。品种之间比较，细毛羊GHR mRNA出现高峰晚于粗毛羊，135日龄高峰时显著地高于粗毛羊；粗毛羊IGF—1、IGF-1RmRNA在90日龄出现高峰，并极显著或显著地高于细毛羊；粗毛羊90日龄前GHR、IGF-1和IGF-1RmRNA高于细毛羊，之后低于细毛羊。结果提示：绵羊皮肤中GHR，IGF-1和IGF-1R基因表达有特定的发育模式，并存在品种差异。

鼻咽癌中IGF-1R、p-ERK、c-fos和Ki-67蛋白的表达及意义

目的研究胰岛素样生长因子1受体(IGF-1R)蛋白与细胞增殖相关信号分子p-ERK、c-fos、Ki-67蛋白在鼻咽癌及鼻咽黏膜上皮细胞中的表达及意义。方法 SP法检测30例鼻咽癌、25例鼻咽黏膜上皮细胞中IGF-1R、p-ERK、c-fos、Ki-67蛋白的表达。结果 IGF-1R、p-ERK、c-fos和Ki-67蛋白在鼻咽癌细胞中阳性表达率分别为93.33%(28/30)、93.33%(28/30)、83.33%(25/30)、86.67%(26/30),在鼻咽黏膜上皮细胞中阳性表达率分别为36.00%(9/25)、28.00%(7/25)、20.00%(5/25)、4.00%(1/25),2组间差异有显著统计学意义(P<0.01);鼻咽癌中IGF-1R与p-ERK、c-fos、Ki-67蛋白阳性表达呈正相关(P<0.05);p-ERK与c-fos、Ki-67蛋白阳性表达呈正相关(P<0.01);c-fos和Ki-67蛋白阳性表达呈正相关(P<0.01)。结论鼻咽癌中IGF-1R蛋白过表达参与调控细胞增殖。

拔毛·剃毛对绵羊皮肤中GHR·IGF-1·IGF-1R·KAP3.2和KAP6-1基因表达的影响

选取36只新疆细毛羊随机分成6组进行拔毛、剃毛处理,于第0、3、6、9、12、50天采集皮肤样品,用反转录多聚酶链式反应(RT-PCR)方法,定量分析绵羊皮肤中生长激素受体(GHR)、胰岛素样生长因子1(IGF-1)和胰岛素样生长因子1型受体(IGF-1R)、角蛋白关联蛋白KAP3.2和KAP6-1mRNA的相对丰度。实验结果显示,与对照组相比,剃毛可显著提高IGF-1的表达量,但对GHR、IGF-1R、KAP3.2和KAP6-1的表达量均无明显的影响;而拔毛对皮肤中GHRI、GF-1I、GF-1R、KAP3.2和KAP6-1基因表达均无明显影响。

蛋用鹌鹑IGF-1R基因的多态性与体尺性状相关性分析

类胰岛素生长因子1型受体(IGF-1R)基因是类胰岛素生长因子(IGFs)在生物体内发挥作用的主要效应器,对机体生长发育进程中有重要影响。为探讨IGF-1R基因多态性与蛋用鹌鹑体尺性状的相关性,采用PCR产物直接测序方法对中国黄羽鹌鹑、北京白羽鹌鹑、朝鲜鹌鹑3种蛋用鹌鹑的IGF-1R基因进行多态性分析,并对IGF-1R基因的多态性与鹌鹑体尺性状进行相关性分析。结果表明,在3个蛋用鹌鹑群体中检测到IGF-1R基因A57G和A72T两个突变位点,A57G位点发生了A/G碱基突变,有AA、AG和GG三种基因型;A72T位点发生了A/T碱基突变,有AA、AT和TT三种基因型。中国黄羽鹌鹑的A57G位点对胫长、胸骨长和胫围有显著影响(P<0.05),A72T位点对体质量和胸骨长有显著影响(P<0.05),组合基因型AGAA对体质量有显著影响(P<0.05),组合基因型AAAA对胫长、胸骨长、胫围有明显影响(P<0.05)。北京白羽鹌鹑的A57G位点对体质量、胫长、体长、胫围有显著影响(P<0.05),A72T位点对胸骨长有显著影响(P<0.05),组合基因型AAAA对体质量和胸骨长有显著影响(P<0.05),组合基因型AAAT、GGAA、GGAT对胫长有显著影响(P<0.05),组合基因型GGAA对胸深有显著影响(P<0.05)。朝鲜鹌鹑的A57G位点对体质量有显著影响(P<0.05),A72T位点对胸骨长和胫围有显著影响(P<0.05),组合基因型AGAA对体质量有显著影响(P<0.05),组合基因型AGAT对胫长和胸宽有显著影响(P<0.05)。因此,IGF-1R基因可以作为候选基因应用于蛋用鹌鹑体尺性状的分子标记辅助选择。

玉米须多糖对糖尿病肾病小鼠IGF-1R和Grb10表达的影响

目的:通过研究玉米须多糖对糖尿病肾病小鼠尿糖、尿蛋白及肾脏IGF-1R和Grb10蛋白表达的影响,探讨玉米须多糖对于糖尿病肾病保护作用的分子机制。方法:腹腔注射链脲菌素(streptozotocin, STZ)建立糖尿病肾病模型,血糖试纸检测小鼠血糖,酶联免疫法检测尿蛋白,western blot法对比正常组、正常组+玉米须多糖组、模型组、模型组+玉米须多糖组小鼠肾脏p-IGF-1R、t-IGF-1R、Grb10蛋白表达。结果:模型组血糖、尿蛋白与正常组相比均明显增高,玉米须多糖干预组与模型组相比血糖、尿蛋白明显降低,差异有统计学意义(P<0.05);p-IGF-1R在模型组表达明显低于正常组,在模型组+玉米须多糖组中表达明显高于模型组,差异有统计学意义(P<0.05)。Grb10在模型组表达明显高于正常组,在模型组+玉米须多糖组中表达明显低于模型组,差异有统计学意义(P<0.05)。结论:玉米须多糖可能通过影响IGF-1R信号通路中IGF-1R的活性和Grb10蛋白的表达,达到改善糖尿病肾病肾脏功能、保护肾脏的作用。

IGF-1R基因多态性与原发性肝癌易感性的相关性研究

目的探讨广西肝癌高发区肝癌相关基因IGF-1R基因多态性与原发性肝癌易感性的关系。方法采用病例对照研究方法,在广西肝癌高发现场人群中选取113例原发性肝癌及113名健康对照人群。以筛选IGF-1R基因SNPrs61740868位点为遗传标志,采用聚合酶链式反应-限制性片段长度多态性方法(PCR-RFLP法)检测IGF-1R基因rs61740868多态性及其基因分布的频率。结果肝癌病例组与对照组IGF-1R基因rs61740868位点均未发生基因突变,其基因型均为CC型,两组比较差异无统计学意义(P>0.05)。结论 IGF-1R基因rs61740868位点多态性与肝癌发生无关,可能不是肝癌的危险因素之一。

血清sFLT1、CTRP3水平与子宫内膜异位症的相关性

目的探究血清可溶性血管内皮生长因子受体1(soluble vascular endothelial growth factor receptor-1,sFLT1)、C1q/肿瘤坏死因子相关蛋白3(C1q/tumor necrosis factor related protein 3,CTRP3)与子宫内膜异位症(endometriosis,EMT)的相关性。方法回顾性分析江西省景德镇市妇幼保健院收治的80例EMT患者(EMT组),依据r-AFS分期分为Ⅰ-Ⅱ期43例,Ⅲ-Ⅳ期37例,按痛经程度分为轻度46例,中-重度34例;对照组为同时间段健康体检女性80例;检测并分析两组血清sFLT1、CTRP3水平,多因素logistic回归分析Ⅲ-Ⅳ期EMT影响因素,受试者工作特征曲线(receiver operating characteristic curve,ROC)评价血清s FLT1、CTRP3对Ⅲ-Ⅳ期EMT诊断价值。结果EMT组患者血清sFLT1、CTRP3水平低于对照组(P<0.05);中-重度痛经者血清sFLT1、CTRP3水平低于轻度者(P<0.05);r-AFS分期Ⅲ-Ⅳ期患者血清sFLT1、CTRP3水平低于Ⅰ-Ⅱ期者(P<0.05);EMT患者血清sFLT1、CTRP3分别与r-AFS分期、痛经程度呈负相关(P<0.05)。回归分析显示,sFLT1、CTRP3是Ⅲ-Ⅳ期EMT影响因素(P<0.05);血清sFLT1、CTRP3及联合诊断Ⅲ-Ⅳ期EMT的AUC为0.811、0.832、0.931,联合诊断效能优于sFLT1、CTRP3单独诊断。结论EMT患者血清sFLT1、CTRP3水平均降低,与痛经程度、r-AFS分期相关,是Ⅲ-Ⅳ期EMT影响因素,二者联合可辅助评估r-AFS分期。

鸡IGF-1R基因序列变异与骨骼、体重性状的相关研究

以东北农业大学F2资源群体为试验材料,采用PCR-RFLP和PCR-SSCP对胰岛素样生长因子-1受体（IGF-1R）基因130 936 bp区域内的7个多态性位点（g.26636C〉T、g.101698A〉G、g.111012C〉G、g.115412A〉C、g.115463T〉C、g.123900G〉A和g.130936T〉C）进行多态性检测和基因分型,利用Haploview软件对IGF-1R基因进行tag SNPs筛选。结果显示,g.26636C〉T、g.101698A〉G、g.111012C〉G、g.115412A〉C和g.115463T〉C多态性位点为IGF-1R基因的tag SNPs;g.115463T〉C、g.123900G〉A和g.130936T〉C 3个多态性位点彼此之间强连锁,处于一个单倍型块中（r2〉0.8）,g.115463T〉C是单倍型块的tag SNP。进一步研究tagSNPs对鸡生长和体组成性状的影响,发现g.115463T〉C对绝大部分骨骼和体重性状有显著或接近显著的影响。因此推断影响鸡骨骼生长发育和6~12周龄体重的QTL可能位于此单倍型块内或处于与此单倍型块紧密连锁的下游区域。

胰岛素样生长因子-1受体(IGF-1R)在非小细胞肺癌组织中的表达及临床意义

目的:评估非小细胞肺癌(NSCLC)细胞中胰岛素样生长因子-1受体(IGF-1R)表达水平,并探讨其与临床特征和生存率的关系。方法:78例NSCLC患者均接受肺癌完全性切除术,NSCLC患者的病理标本采用免疫组织化学法染色检测IGF-1R在NSCLC组织中的表达,并进行染色细胞的百分比评分及染色强度评分。将评分相加,大于3分样本被分类为高表达,反之为低表达。结果:IGF-1R高表达与淋巴结转移和复发相关(P=0.034,P=0.006)。IGF-1R高表达较IGF-1R低表达与显著降低总体生存率相关(P=0.011)。经多因素分析,IGF-1R表达与NSCLC患者预后独立相关。结论:IGF-1R的过表达可能是NSCLC患者淋巴结转移、复发和术后预后的一个有效的预测因子。

IGF-1R抗体对兔耳瘢痕组织的影响

目的:观察胰岛素样生长因子-1受体(IGF-1R)抗体对兔耳增生性瘢痕组织的影响。方法:建立兔耳增生性瘢痕动物模型,21天后瘢痕局部注射不同浓度的IGF-1R抗体或生理盐水,连续7天,观察1个月。分别对瘢痕增生指数(hypertrophicindex,HI)、成纤维细胞数和胶原含量的变化进行比较。结果:一定剂量IGF-1R抗体组HI值、成纤维细胞数量以及胶原含量比对照组减少(P<0.01或0.05)。结论:IGF-1R抗体能抑制兔耳瘢痕组织增生。

Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection. Insulin-like growth factor 1 receptor (IGF-1R) signaling plays a very important role in progression, invasion and metastasis of bladder cancer cells. In this study, we investigated whether IGF-1R was involved in the growth stimulating activity and drug resistance of bladder cancer cells. The results showed: The mRNAs of IGF-1, IGF-2 and IGF-1R were strongly expressed in serum-free cultured T24 cell line, whereas normal urothelial cells did not express these factors/receptors or only in trace levels; T24 cell responded far better to growth stimulation by IGF-1 than did normal urothelial cells; blockage of IGF1R by antisense oligodeoxynucleotide (ODN) significantly inhibited the growth of T24 cell and enhanced sensitivity and apoptosis of T24 cells to mitomycin (MMC). These results suggested that blockage of IGF-IR signaling might potentially contribute to the treatment of bladder cancer cells which are insensitive to chemotherapy.